Water pipe smoking (WPS), an old method of tobacco smoking, is re-gaining widespread popularity all over the world and among various populations. Smoking machine studies have shown that the water pipe (WP) mainstream smoke (MSS) contains a wide array of chemical substances, many of which are highly toxic and carcinogenic for humans. The concentrations of some substances exceed those present in MSS of cigarettes. Despite being of low grade, current evidence indicates that WPS is associated with different adverse health effects, not only on the respiratory system but also on the cardiovascular, hematological, and reproductive systems, including pregnancy outcomes. In addition, association between WPS and malignancies, such as lung, oral and nasopharyngeal cancer, has been suggested in different studies and systematic reviews. Despite its long standing history, WPS research still harbors a lot of deficiencies. The magnitude of toxicants and carcinogen exposures, effects on human health, as well as the addiction and dependence potentials associated with WPS need to be studied in well-designed prospective trials. Unfortunately, many of the tobacco control and clean indoor policies have exempted water pipes. World wide awareness among the public, smokers, and policymakers about the potential health effects of WPS is urgently required. Furthermore, stringent policies and laws that control and ban WPS in public places, similar to those applied on cigarettes smoking need to be implemented.